Title:Decoding Common Features of Neurodegenerative Disorders: From Differentially Expressed Genes to Pathways
Volume: 19
Issue: 4
Author(s): Rabia Habib, Nighat Noureen*Neha Nadeem
Affiliation:
- Biosciences Department, COMSATS Institute of Information Technology, Islamabad,Pakistan
Keywords:
Neurodegeneration, Alzheimer's, Parkinson's, Frontotemporal dementia, Amyotrophic lateral sclerosis, Dysregulated
genes, Retrograde endocannabinoid signaling, Calcium signaling.
Abstract: Background: Neurodegeneration is a progressive/irreversible loss of neurons, building
blocks of our nervous system. Their degeneration gradually collapses the entire structural and functional
system manifesting in myriads of clinical disorders categorized as Neurodegenerative Disorders
(NDs) such as Alzheimer's Disease, (AD), Parkinson’s Disease (PD), Frontotemporal Dementia
(FTD) and Amyotrophic Lateral Sclerosis (ALS). NDs are characterized by a puzzling interplay of
molecular and cellular defects affecting subset of neuronal populations in specific affected brain areas.
Objective: In present study, comparative in silico analysis was performed by utilizing gene expression
datasets of AD, PD, FTD and ALS to identify potential common features to gain insights into complex
molecular pathophysiology of the selected NDs.
Methods: Gene expression data of four disorders were subjected to the identification of Differential
Gene Expression (DEG) and their mapping on biological processes, KEGG pathways and molecular
functions. Detailed comparative analysis was performed to highlight the common grounds of these
disorders at various stages.
Results: Astoundingly, 106 DEGs were found to be common across all disorders. Alongwith in total
100 GO terms and 7 KEGG pathways were found to be significantly enriched across all disorders.
EGFR, CDC42 and CREBBP have been identified as the significantly interacting nodes in gene-gene
interaction and in Protein-Protein Interaction (PPI) network as well. Furthermore, interaction of common
DEGs targets with miRNA’s has been scrutinized.
Conclusion: The complex molecular underpinnings of these disorders are currently elusive. Despite
heterogeneous clinical and pathological expressions, common features have been recognized in many
NDs which provide evidence of their convergence.
